Search

Objective: To analyze the factors associated with survival in the largest cohort of individuals with HIV and lymphoma so far described in Brazil., Design: A retrospective, observational, multicenter study involving five institutions in São Paulo, Brazil., Methods: The medical records of consecutive patients with HIV diagnosed with lymphoma between January 2000 and December 2019 were screened. Inclusion criteria consisted of age over 17 years and a biopsy-confirmed diagnosis of lymphoma. The data collected included age, sex, staging (Ann Arbor system), duration of HIV infection, CD4 + lymphocyte count, HIV viral load, lactate dehydrogenase, erythrocyte sedimentation rate and serum beta-2-microglobulin levels, treatment and outcome., Results: Overall, 276 patients were included. Median age was 42 years. Most patients were male (74.3%) and with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (28.6% and 46.4%, respectively). Most had non-Hodgkin lymphomas (89.2%, n  = 246), particularly diffuse large B-cell lymphoma (40.9%) and Burkitt lymphoma (26.4%). Hodgkin lymphoma accounted for 9.4%. Advanced stages III/IV were predominant (86.8%). HIV viral load at the moment of lymphoma diagnosis was detectable in 52.9% of patients. A CD4 + cell count of <200 cells/μl was recorded for 53% of the patients. Most patients (62.4%) were on combination antiretroviral therapy. The factors that significantly affected survival were: the ECOG performance status, lymphoma subtype, staging, beta-2-microglobulin level, central nervous system (CNS) infiltration, site of CNS infiltration, relapsed/refractory lymphoma and International Prognostic Index score., Conclusions: HIV status, CD4 + -lymphocyte count and relapsed/refractory disease affected survival. Rituximab did not appear to improve outcome in HIV-related lymphomas., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) is a preferred regimen for HIV-non-Hodgkin lymphomas (HIV-NHLs), which are frequently Epstein-Barr virus (EBV) positive or human herpesvirus type-8 (HHV-8) positive. The histone deacetylase (HDAC) inhibitor vorinostat disrupts EBV/HHV-8 latency, enhances chemotherapy-induced cell death, and may clear HIV reservoirs. We performed a randomized phase 2 study in 90 patients (45 per study arm) with aggressive HIV-NHLs, using dose-adjusted EPOCH (plus rituximab if CD20+), alone or with 300 mg vorinostat, administered on days 1 to 5 of each cycle. Up to 1 prior cycle of systemic chemotherapy was allowed. The primary end point was complete response (CR). In 86 evaluable patients with diffuse large B-cell lymphoma (DLBCL; n = 61), plasmablastic lymphoma (n = 15), primary effusion lymphoma (n = 7), unclassifiable B-cell NHL (n = 2), and Burkitt lymphoma (n = 1), CR rates were 74% vs 68% for EPOCH vs EPOCH-vorinostat (P = .72). Patients with a CD4+ count <200 cells/mm3 had a lower CR rate. EPOCH-vorinostat did not eliminate HIV reservoirs, resulted in more frequent grade 4 neutropenia and thrombocytopenia, and did not affect survival. Overall, patients with Myc+ DLBCL had a significantly lower EFS. A low diagnosis-to-treatment interval (DTI) was also associated with inferior outcomes, whereas preprotocol therapy had no negative impact. In summary, EPOCH had broad efficacy against highly aggressive HIV-NHLs, whereas vorinostat had no benefit; patients with Myc-driven DLBCL, low CD4, and low DTI had less favorable outcomes. Permitting preprotocol therapy facilitated accruals without compromising outcomes. This trial was registered at www.clinicaltrials.gov as #NCT0119384., (© 2020 by The American Society of Hematology.)

People living with HIV (PLHIV) are more likely than the general population to develop AIDS-defining malignancies (ADMs) and several non-ADMs (NADMs). Information is lacking on survival outcomes and cause-specific mortality after cancer diagnosis among PLHIV. We investigated causes of death within 5 years of cancer diagnosis in PLHIV enrolled in European and North American HIV cohorts starting antiretroviral therapy (ART) 1996-2015, aged ≥16 years, and subsequently diagnosed with cancer. Cancers were grouped: ADMs, viral NADMs and nonviral NADMs. We calculated cause-specific mortality rates (MR) after diagnosis of specific cancers and compared 5-year survival with the UK and France general populations. Among 83,856 PLHIV there were 4,436 cancer diagnoses. Of 603 deaths after ADM diagnosis, 292 (48%) were due to an ADM. There were 467/847 (55%) and 74/189 (39%) deaths that were due to an NADM after nonviral and viral NADM diagnoses, respectively. MR were higher for diagnoses between 1996 and 2005 versus 2006-2015: ADMs 102 (95% CI 92-113) per 1,000 years versus 88 (78-100), viral NADMs 134 (106-169) versus 111 (93-133) and nonviral NADMs 264 (232-300) versus 226 (206-248). Estimated 5-year survival for PLHIV diagnosed with liver (29% [19-39%]), lung (18% [13-23%]) and cervical (75% [63-84%]) cancer was similar to general populations. Survival after Hodgkin's lymphoma diagnosis was lower in PLHIV (75% [67-81%]). Among ART-treated PLHIV diagnosed with cancer, MR and causes of death varied by cancer type, with mortality highest for liver and lung cancers. Deaths within 5 years of NADM diagnoses were more likely to be from cancer than AIDS., (© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Objective: Chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infections are associated with increased risks of lymphomas in the non-HIV setting. Their impacts on HIV-associated lymphomas deserved further studies in the modern combined antiretroviral therapy (cART) era., Design: We evaluated the associations between HCV, HBV and HIV-related lymphomas in the Lymphovir-ANRS-CO16 cohort., Methods: Prevalence of HCV seropositivity and chronic HBV infections were compared with those observed in the French Hospital Database on HIV (FHDH-ANRS-CO4)., Results: Between 2008 and 2015, 179 patients with HIV-related lymphomas from 32 French hospitals were enrolled, 69 had Hodgkin's lymphoma (39%), and 110 non-Hodgkin's lymphoma (NHL) (61%). The prevalence of HCV infection was higher in patients with NHL than in the FHDH-ANRS-CO4 [26 versus 14%, odd ratio (OR): 2.15; 95% confidence interval (1.35-3.32)] whereas there was no association between Hodgkin's lymphoma and chronic HCV infection. Chronic HBV infection was not associated with NHL in our cohort with a prevalence of 5 versus 7% in FHDH-ANRS-CO4 but tended to be associated with Hodgkin's lymphoma [prevalence of 14%, OR: 2.16 (0.98-4.27)]. Chronic HCV infection tended to pejoratively impact 2-year overall survival in patients with NHL: 72% [57%, 91%] versus 82% [74%, 91%], hazard ratio: 2.14 [0.95-4.84]. In contrast, chronic HBV infection did not correlate with outcome., Conclusion: In the modern cART era, chronic HCV infection is associated with an increased risk of NHL in PLWHIV and tends to pejoratively impact overall survival. HBV infection is not associated with the risk of NHL but with a borderline increase of Hodgkin's lymphoma risk.

Background: Malignant lymphoma is still the leading cause of death among AIDS-related diseases., Patients and Methods: We performed a retrospective analysis of 50 HIV-positive lymphoma patients. The median interval between HIV and malignant lymphoma diagnosis was 4 years. Eight patients (16%) had Hodgkin lymphoma and 42 (84%) non-Hodgkin lymphoma. Among non-Hodgkin lymphoma patients, diffuse large B-cell lymphoma (n = 18, 42%), Burkitt lymphoma (n = 11, 26%), and plasmoblastic lymphoma (n = 5, 12%) were the most frequent entities., Results: Lymphoma was treated according to standard protocols. Forty-four patients (88%) received combination antiretroviral therapy, 2 (4%) were not treated, and in 4 (8%) the HIV treatment status was not clarified. Response to first-line therapy was complete response (CR) in 24 (56%), partial response (PR) in 15 (35%), and stable disease in 1 (2%). Three patients (7%) developed progressive disease, and 9 (18%) experienced relapse after CR or PR. At a median observation period of 31 (range, 0.4-192) months, the 1-, 2-, and 5-year overall survival was 87%, 79%, and 76%, respectively. At univariate analysis, remission status after first-line treatment was predictive of outcome, as the 2-year overall survival was 95%, 66%, and 0 for patients with CR, with PR, and with progressive disease (P < .001). Results of the multivariate analysis revealed lactate dehydrogenase concentration at lymphoma diagnosis (P = .046) and relapse (P = .050) to be independent factors for overall survival., Conclusion: First-line treatment of lymphoma in HIV positive patients is crucial. Patients who experienced and maintained a first CR had a favorable prognosis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: HIV-infected patients are more than 100-fold greater at risk for developing malignant AIDS-related lymphoma (ARL) compared to the general population. Most ARLs are EBV related. The main purpose of this study was to investigate whether a high peak EBV DNA load in HIV-infected patients is predictive of ARL, including classical Hodgkin lymphoma., Methods: From an ongoing prospective HIV positive cohort study, we conducted a case-control study between 2004 and 2016 among patients from whom at least one EBV DNA load in serum or plasma was available. We compared peak EBV DNA load between patients with (49 cases) and without ARL (156 controls)., Results: The geometric mean of the peak EBV DNA load measured before diagnosis of malignant lymphoma was 52,565 IU/mL in EBER-positive lymphoma patients vs. 127 IU/mL in controls (p < .001). Patients with EBV DNA loads >100,000 IU/mL have an increased risk for diagnosis of malignant lymphoma compared to patients with EBV DNA loads ≤100,000 IU/mL (adjusted OR 12.53; 95%CI: 4.08; 38.42). In the longitudinal study, including 13 patients with at least three left-over plasma samples available for retesting, measurements of EBV-DNA during the preceding 12 months proved to be of poor value for predicting subsequent lymphoma diagnosis., Conclusions: A EBV DNA load >100,000 IU/mL can be useful in clinical setting to accelerate time to diagnosis and treatment. EBV-DNA loads in samples taken during the preceding year of ARL diagnosis showed to be of poor predictive value.

Background: We report the first case to our knowledge of a patient with relapsed/refractory classical hodgkin lymphoma and liver failure with encephalopathy along with human immunodeficiency virus/acquired immunodeficiency syndrome infection, successfully treated with nivolumab without major side effects and encouraging prolonged disease control., Case Presentation: In December 2015, at the time of the patient's progression from his Hodgkin lymphoma after fourth line treatment, he developed persistent fevers, abdominal distension, jaundice and worsening of his liver function tests. Magnetic resonance imaging of abdomen/pelvis demonstrated hepatomegaly with innumerable new liver lesions, splenomegaly with multiple splenic nodules and several new mediastinal, intraperitoneal and retroperitoneal lymphadenopathy. In accordance with the patient's wishes before admission, and after agreement with the family, nivolumab (3 mg/kg every 2 weeks) was given. Of note, antiretroviral therapy was on hold due to liver function tests, his viral load was undectable and cluster of differentiation 4 counts were 103/uL at the time of nivolumab administration. One week after the first dose of nivolumab both his hepatic encephalopathy and constitutional symptoms started to improve, and after 2 doses, (January 2016) his LFTs were almost back to normal. After 5 months of nivolumab treatment (10 doses), restaging (computerized tomography scans of neck, chest, abdomen, pelvis) done on May 2016 showed resolution of hepatosplenomegaly with two residual small hepatic lesions, heterogeneous spleen with no splenic lesions, and stable non-enlarged retroperitoneal lymph nodes without intraabdominal lymphadenopathy; consistent with partial response., Conclusions: We report a case of a patient with human immunodeficiency virus/acquired immunodeficiency syndrome -related relapsed/refractory classical Hodgkin lymphoma and acute liver failure with encephalopathy successfully treated with nivolumab after failing all standard therapeutic options. Unlike classic cytotoxic chemotherapy, which relies on preserved organ function to ameliorate potential severe side effects (i.e. myelosuppression), elimination of monoclonal antibodies is fairly independent of baseline renal and hepatic function since they are usually metabolized by circulating phagocytes and/or by their target antigen-expressing cell.

Plasmablastic lymphoma is a rare and aggressive B cell lymphoma that is considered to be strongly associated with HIV infection. This article explores the histological morphology and immunohistochemical characteristics of HIV/AIDS-related plasmablastic lymphoma with the goal of improving the diagnosis and treatment of this rare tumor. According to criteria of the World Health Organization Classification of Tumors of Hematopoietic and Lymphoid Tissues (2008), six plasmablastic lymphoma cases admitted to the Shanghai Public Health Clinical Center were comprehensively analyzed with conventional hematoxylin-eosin staining, immunohistochemical staining and in situ hybridization. The morphological features of six tumors were consistent with PBL. Immunohistochemical staining showed that all six cases were negative for CD19, CD20, and CD79a, and positive for OCT-2, BOB-1, VS38c, and melanoma ubiquitous mutated 1. The Ki67 proliferation index was higher than 90% in all six cases. In situ hybridization indicated that four cases were EBER-positive. In addition, three cases had C-MYC translocation rearrangement. Our results showed that the immunophenotypes of PBL vary, which makes PBL diagnosis difficult. Therefore, morphological characteristics, immunophenotypic markers, and clinical data should be used in combination to enable an accurate diagnosis, especially in the presence of immunophenotypic variation, as this approach will facilitate timely treatment.

Central nervous system (CNS) involvement is reportedly more common in acquired immunodeficiency syndrome (AIDS)-related lymphomas (ARL). We describe factors and outcomes associated with CNS involvement at baseline (CNS(B) ) and relapse (CNS(R) ) in 886 patients with newly diagnosed ARL. Of 886 patients, 800 received either intrathecal (IT) therapy for CNS(B) or IT prophylaxis. CNS(B) was found in 13%. CNS(B) was not associated with reduced overall survival (OS). There was no difference in the prevalence of CNS(B) between the pre-combination antiretroviral therapy (cART) and cART eras. 5·3% of patients experienced CNS(R) at a median of 4·2 months after diagnosis (12% if CNS(B) ; 4% if not). Median OS after CNS(R) was 1·6 months. On multivariate analysis, only CNS(B) [hazard ratio (HR) 3·68, P = 0·005] and complete response to initial therapy (HR 0·14, P < 0·0001) were significantly associated with CNS(R) . When restricted to patients without CNS(B) , IT CNS prophylaxis with 3 vs. 1 agent did not significantly impact the risk of CNS(R) . Despite IT CNS prophylaxis, 5% of patients experienced CNS(R) . Our data confirms that CNS(R) in ARL occurs early and has a poor outcome. Complete response to initial therapy was associated with a reduced frequency of CNS(R) . Although CNS(B) conferred an increased risk for CNS(R) , it did not impact OS., (© 2016 John Wiley & Sons Ltd.)

Classically, the HIV/AIDS-related lymphomas are of the B cell type and involve the central nervous system and the abdominal cavity. Primary maxillary sinus lymphoma is rare. Plasmablastic lymphoma (PBL) is an aggressive form of non-Hodgkinvs lymphoma, and is extremely rare. Here we present a case of plasmablastic lymphoma with primary site being maxillary sinus, a rare location., (© Journal of the Association of Physicians of India 2011.)

Hodgkin lymphoma (HL) is more frequent in patients with Human Immunodeficiency Virus (HIV) infection than in immunocompetent patients. The relationship between the immune system and HL is complex. Whilst the incidence of HL in HIV patients has most likely increased since the introduction of combined anti-retroviral therapy (cART), there is no doubt that the outcomes for patients with HIV and HL (HIV-HL) have improved since its introduction. Improved CD4 counts and risk-adapted treatment schedules have resulted in outcomes for patients with HIV-HL that are comparable to those in HIV-negative patients with HL. Thus, HIV-HL should be treated in the same way as HL in immunocompetent patients, including the use of salvage chemotherapy and autologous transplant in the relapsed setting in HIV-HL. Along the same lines, patients with HIV-HL should not be excluded from trials based on their immune status alone.

A 44-year-old patient, with personal history of AIDS, was referred to our emergency unit with tachycardia and moderate signs of right-sided heart failure. The cardiac MRI study showed an impairment of the right ventricular free and inferior wall and the interventricular septum. The mass was characterized by notable heterogeneity with mixed areas of hypo- and hypersignal intensity in SSFP and T2-weighted images with fat saturation. There was global hyperenhancement of the mass after gadolinium contrast injection on T1-weighted images with and without fat saturation. The entire right coronary artery was included into the infiltrative mass. One day after the admission, the patient suddenly presented a paroxysmal third degree atrioventricular block, permanently corrected by an implanted cardiac pacemaker. Endomyocardial biopsy conformed the diagnosis of B-cell lymphoma. The patient died 4months after the diagnosis of acute heart failure with multi-organ dysfunction, after a short period of improvement under chemotherapy. We present this case to highlight the importance to consider that a large, solitary, right atrial mass in conjunction with pericardial effusion in a patient with HIV infection should lead to consider, as soon as possible, the diagnosis of lymphoma. MRI has explained the conduction disorders by showing the septal extension of the mass, and by demonstrating right coronary artery involvement., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Limited comparative data exist for the treatment of HIV-associated non-Hodgkin lymphoma. We analyzed pooled individual patient data for 1546 patients from 19 prospective clinical trials to assess treatment-specific factors (type of chemotherapy, rituximab, and concurrent combination antiretroviral [cART] use) and their influence on the outcomes complete response (CR), progression free survival (PFS), and overall survival (OS). In our analysis, rituximab was associated with a higher CR rate (odds ratio [OR] 2.89; P < .001), improved PFS (hazard ratio [HR] 0.50; P < .001), and OS (HR 0.51; P < .0001). Compared with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), initial therapy with more dose-intense regimens resulted in better CR rates (ACVBP [doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisolone]: OR 1.70; P < .04), PFS (ACVBP: HR 0.72; P = .049; "intensive regimens": HR 0.35; P < .001) and OS ("intensive regimens": HR 0.54; P < .001). Infusional etoposide, prednisone, infusional vincristine, infusional doxorubicin, and cyclophosphamide (EPOCH) was associated with significantly better OS in diffuse large B-cell lymphoma (HR 0.33; P = .03). Concurrent use of cART was associated with improved CR rates (OR 1.89; P = .005) and trended toward improved OS (HR 0.78; P = .07). These findings provide supporting evidence for current patterns of care where definitive evidence is unavailable.

A 43-year-old man known case of retropositive illness presented with abdomen pain of 15 days and loose stools for 10 days. Loose stools were foul smelling and blood stained. The patient was a known case of type 2 diabetes and retroviral illness on highly active antiretroviral therapy (HAART). General physical examination was normal. On examination an irregular mass was palpable in the right iliac fossa and right flank. The mass was hard in nature; irregular with restricted mobility. There was no palpable liver or spleen. CT of the abdomen and pelvis revealed a well-defined heterogeneously enhancing hypodense mass lesion measuring 16 × 11.7 × 12 cm involving the ileocaecal region and extending medially and inferiorly to sigmoid colon and rectum. A colonoscopy showed a proliferative highly vascular mass 15 cm from anal verge at the rectosigmoid junction. Histopathology revealed sheets of neoplastic lymphoid cells in rectal wall suggestive of non-Hodgkins lymphoma.

Background: The objective of this study was to compare immunologic, virologic, and clinical outcomes between living human immunodeficiency virus (HIV)-infected individuals who had a diagnosis of lymphoma versus outcomes in a control group of cancer-free, HIV-infected patients., Methods: In this matched cohort study, patients in the case group were survivors of incident lymphomas that occurred between 1997 and June 2010. Controls were living, cancer-free, HIV-infected patients who were matched to cases at a 4:1 ratio by age, sex, nadir CD4 cell count, and year of HIV diagnosis. The date of lymphoma diagnosis served as the baseline in cases and in the corresponding controls., Results: In total, 62 patients (cases) who had lymphoma (20 with Hodgkin disease [HD] and 42 with non-Hodgkin lymphoma [NHL]) were compared with 211 controls. The overall median follow-up was 4.8 years (interquartile range, 2.0-7.9 years). The CD4 cell count at baseline was 278 cells/mm³ (interquartile range, 122-419 cells/mm³) in cases versus 421 cells/mm³ (interquartile range, 222-574 cells/mm³) in controls (P = .003). At the last available visit, the CD4 cell count was 412 cells/mm³ (range, 269-694 cells/mm³) in cases versus 518 cells/mm³ (interquartile range, 350-661 cells/mm³) in controls (P = .087). The proportion of patients who achieved virologic success increased from 30% at baseline to 74% at the last available visit in cases (P = .008) and from 51% to 81% in controls (P = .0286). Patients with HD reached higher CD4 cell counts at their last visit than patients with NHL (589 cells/mm³ [range, 400-841 cells/mm³] vs 332 cells/mm³ [interquartile range, 220-530 cells/mm³], respectively; P = .003). Virologic success was similar between patients with HD and patients with NHL at the last visit. Forty cases (65%) and 76 controls (36%) experienced at least 1 clinical event after baseline (P < .0001); cases were associated with a shorter time to occurrence of the first clinical event compared with controls (P < .0001)., Conclusions: HIV-infected lymphoma survivors experienced more clinical events than controls, especially during the first year of follow-up, but they reached similar long-term immunologic and virologic outcomes., (© 2013 American Cancer Society.)

Hepatitis C virus (HCV) infection is frequent among HIV-infected patients. We describe, the characteristics of 6 HIV/HCV-coinfected patients with B-cell non-Hodgkin lymphoma (NHL) included in a prospective cohort study of HIV-related lymphomas. Five of the 6 cases had features of marginal zone/lymphoplasmacytic NHL versus 1 of 33 HIV only-infected patients. Remarkably, anti-HCV treatment led to a hematological response in a patient with splenic marginal zone lymphoma. This supports the role of chronic antigenic stimulation by HCV on lymphomagenesis and further evaluation of HCV antiviral therapy in coinfected patients with NHL.

HIV-infected patients are at increased risk for developing HIV-related Hodgkin lymphoma (HIV-HL) despite the success of combination antiretroviral therapy (cART). To study the incidence of HIV-HL in HIV-patients with respect to the general population of Brescia, Italy, we conducted a single-center cohort study of HIV-patients followed from 1999 to 2009. The incidence of HIV-HL was compared to the incidence in the general population of Brescia using standardized incidence ratios (SIRs). Poisson analysis was used to study the association between covariates and HL. A total of 5085 HIV-patients were observed among 30,946 person-years; 30 patients developed HIV-HL. The incidence rate was 9.9 (95% confidence interval [CI], 6.7-14.1) per 10,000 person-years of follow-up. HL was substantially more frequent in HIV-patients than in the general population living in the same district area [standardized incidence rate, SIR=21.8 (95% CI, 15.33-31)]. The risk of HIV-HL tended to increase with lowering CD4+ cell counts at time of HL diagnosis [adjusted incidence relative risk (IRR) for CD4 cell count<50 cells/μL: 41.70, p<0.001]. HL risk had been elevated during the 6 months after combination antiretroviral therapy (cART) initiation (IRR: 26.65, p<0.001). Twenty-two HIV-HL cases were matched to 3280 controls. In the year preceding HIV-HL diagnosis the mean change in CD4+ cell counts between cases and controls was significantly different (-99 cells/μL for cases vs. +37 cells/μL for controls, p<0.0001). Compared with the general population, HIV-infected patients showed an increased risk for developing HL. The risk of HIV-HL increased significantly in the first months after cART initiation.

Immune reconstitution inflammatory syndrome (IRIS) is associated with clinical manifestations that can overlap with the patients with acquired immunodeficiency disease (AIDS)-related non-Hodgkin's lymphoma. We herein report a case of AIDS-related Burkitt lymphoma which was successfully treated with dose-adjusted etoposide, doxorubicin, cyclophosphamide, vincristine, and prednisone (EPOCH). However, the patient developed a lymphoma-like clinical presentation shortly after the conclusion of chemotherapy. The patient's symptoms were identical to the initial symptoms characteristic of lymphoma; however, the laboratory data revealed no evidence of a relapse of Burkitt lymphoma. A bone marrow examination showed T-cell clonality, even though there were no signs of any progression of the lymphoma. The patient was diagnosed with IRIS, and the clinical manifestations rapidly improved following treatment.

We evaluated risk factors for neutropenic fever and febrile prolonged neutropenia during vincristine-including chemotherapy to treat HIV-related lymphoma to investigate whether protease inhibitor (PI) treatment is associated with infectious complications due to drug interactions with chemotherapeutic agents. We included all HIV patients who received chemotherapy including vincristine for lymphoma at a single referral center in 1999-2010. Neutropenic fever was defined as absolute neutrophil count < 500 cells/µL with body temperature over 38℃; and prolonged neutropenia was defined if it persisted over 7 days. CODOX-M/IVAC and Stanford regimens were considered high-risk regimens for prolonged neutropenia. We analyzed 48 cycles of chemotherapy in 17 HIV patients with lymphoma. There were 22 neutropenic fever and 12 febrile prolonged neutropenia events. In multivariate analysis, neutropenic fever was associated with old age and low CD4 cell count, but not with PI use or ritonavir-boosted PI use. Low CD4 cell count and high-risk regimens were associated with febrile prolonged neutropenia. Neutropenic fever and febrile prolonged neutropenia is associated with old age, low CD4 cell count, and high-risk regimens, but not PI use, in HIV patients undergoing chemotherapy including vincristine for lymphoma.

Cardiac onset of a diffuse large B-cell lymphoma (DLBCL) in a HIV+ patient with hypertrophic obstructive cardiomyopathy. The sequence of diagnosis, therapeutical planning and final outcome underlines the importance of an early diagnosis that cannot be conceived without an increased attention in this clinical setting (aspecific symptoms in an HIV positive subject) by the General Practitioner.

Background: AIDS-related lymphoma (ARL) remains the main cause of AIDS-related deaths in the combined antiretroviral therapy (cART) era. Although most ARLs are associated with the Epstein-Barr virus (EBV), whether patients with high EBV burden are more at risk of developing ARL is unknown. This study investigated the relationship between high blood EBV DNA loads and subsequent progression to ARL., Methods: We identified 43 cases of ARL diagnosed between 1988 and 2007 within two cohorts (ANRS SEROCO/HEMOCO and PRIMO) and for which stored serum and peripheral blood mononuclear cell (PBMC) samples were available within 3 years before ARL diagnosis. For each case, two controls matched for the cohort and CD4 cell count in the year of ARL diagnosis were selected. EBV DNA was measured in PBMCs and serum samples with a commercial kit., Results: High levels of EBV DNA in PBMCs collected a median of 10 months before diagnosis were associated with an increased risk of developing systemic B lymphoma (adjusted odds ratio 2.47; 95% confidence interval 1.15; 5.32 for each 1 log copies/10(6) PBMC increase in EBV load) but not with primary brain lymphoma., Conclusion: In this study, HIV-infected patients with undetectable EBV DNA in PBMCs did not develop ARL in the following 3 years, while high levels of EBV DNA in PBMCs predicted subsequent progression to systemic B lymphoma. Clinicians should be aware of the increased risk of developing systemic B lymphoma in HIV-infected patients with a high blood EBV DNA load., (© 2012 British HIV Association.)

Purpose: Epstein-Barr virus (EBV)-mediated lymphomagenesis in the setting of HIV infection has been widely accepted. However, little is known about how EBV impacts prognosis. We investigated the hypothesis that EBV infection is associated with expression of specific B-cell oncogenic markers in HIV-related diffuse large B-cell lymphoma (DLBCL) and examined the prognostic use of detecting EBV infection., Experimental Design: HIV-related DLBCL cases diagnosed between 1996 and 2007 within Kaiser Permanente California were identified. Immunohistochemical staining was used to analyze the expression of selected markers that are cell-cycle regulators, B-cell activators, and antiapoptotic proteins among others. EBV infection was determined by in situ hybridization of EBV RNA. Correlations between EBV and marker expression were examined using Spearman correlation coefficient. The prognostic use of EBV status was examined in multivariable Cox model adjusting for International Prognostic Index (IPI). Receiver-operating characteristics (ROC) analysis was used to evaluate improvement in model discrimination., Results: Seventy HIV-related DLBCL cases were included (31% EBV±). EBV+ tumor was associated with increased expression of BLIMP1 and CD30 and reduced expression of BCL6 and LMO2. EBV+ tumor was independently associated with elevated 2-year overall mortality [HR, 3.3; 95% confidence interval (CI), 1.6-6.6]. Area under the ROC curve showed improved model discrimination when incorporating tumor EBV status with IPI in the prediction model [0.65 vs. 0.74 (IPI only)]., Conclusion: Our results suggest that EBV infection was associated with expression of several tumor markers that are involved in the NF-κB pathway and that detecting tumor EBV status may have prognostic use in HIV-related DLBCLs., (©2012 AACR.)

Epstein-Barr virus (EBV)-associated polymorphic lymphoid proliferations resembling polymorphic post-transplant lymphoproliferative disorders are a rare but recognised complication of the human immunodeficiency virus (HIV). These account for fewer than 5 % of HIV-associated lymphomas, and little information has been published regarding their treatment and outcome. Of the reported cases, many have presented with extranodal disease, not typical of lymphoma. We report the case of a patient presenting with lung infiltrates shown to be the result of an EBV-associated polymorphic lymphoproliferation resembling a polymorphic post-transplant lymphoproliferative disorder. The patient was simultaneously found to be HIV positive and commenced on highly active antiretroviral therapy. Without any specific anti-neoplastic treatment, the patient recovered completely and within 20 months had no symptoms or radiological evidence of a lymphoproliferative disorder. This illustrates the importance of recognising this uncommon condition in HIV-positive patients and avoiding potentially unnecessary chemotherapy.

Objectives: Plasmablastic lymphoma (PBL) of the oral cavity is a rare form of non-Hodgkin lymphoma that is most frequently met in human immunodeficiency (HIV) positive patients. Only a few cases have been reported worldwide since 1997. This clinical entity may escape detection due to its unusual immunophenotype and rare occurrence. Our aim is to present two cases with this rare condition that were diagnosed and treated in our department., Materials and Methods: We describe two cases of PBLs in HIV-infected patients, who presented with an expanding painless oral lesion and summarize the literature in order to elucidate the nature of this malignancy., Results: The first patient received chemotherapy with additional radiotherapy that led to complete remission of the disease, while the second experienced a relapse 6 months after treatment with chemotherapy, that caused his death after refusal of further treatment., Conclusion: Because of the consistent epidemiological association of PBL with immunosuppression, any patient diagnosed with PBL should be tested for HIV. The clinical picture of PBL, including its affinity with HIV-infection, male sex, and its predilection for the oral cavity, may contribute to the differential diagnosis. Any oral mass occurring in an immunosuppressed patient should be referred for biopsy, since the early diagnosis of these tumors leads to better prognosis of the patients.

Unilateral ptosis is seen in a limited number of conditions such as Horner syndrome, cluster headache, trauma, tumor, stroke, old age, nerve injury, lacrimal gland tumor, temporal arteritis or disorders of the upper eyelid. The authors present a case of unilateral ptosis secondary to Burkitt lymphoma metastasis to brain with excellent response to chemotherapy and complete resolution of ptosis in a man with human immunodeficiency virus. This vignette emphasizes the importance of recognizing ptosis as an initial presentation of Burkitt lymphoma in a patient with human immunodeficiency virus under appropriate clinical settings.

Lymphomas that develop in human immunodeficiency virus (HIV) infected patients are predominantly aggressive B-cells lymphomas. The most common HIV-associated lymphomas include Burkitt lymphoma, diffuse large B-cell lymphoma (that often involves the CNS), primary effusion lymphoma, and plasmablastic lymphoma (PBL). Of these, PBL is relatively uncommon and displays a distinct affinity for presentation in the oral cavity. In this manuscript we report a previously undescribed primary leptomeningeal form of PBL in a patient with acquired immunodeficiency syndrome. A 40-year-old HIV positive man presented with acute onset confusion, emesis, and altered mental status. Lumbar puncture showed numerous nucleated cells with atypical plasmocyte predominance. CSF flowcytometry showed kappa restriction with CD8 and CD38 positivity and negative lymphocyte markers, while the MRI showed diffuse leptomeningeal enhancement. As the extensive systemic work-up failed to reveal any disease outside the brain, an en bloc diagnostic brain and meningeal biopsy was performed. The biopsy specimen showed sheets of plasmacytoid cells with one or more large nuclei, prominent nuclear chromatin, scattered mitoses, and abundant cytoplasm, highly suggestive of plasmablastic lymphoma. HIV-associated malignancies have protean and often confusing presentations, which pose diagnostic difficulties posed to the practicing neurological-surgeons. Even in cases where an infectious cause is suspected for the meningeal enhancement, neoplastic involvement should be considered, and cytology and flow-cytometry should be routinely ordered on the CSF samples.

Background: The risk of developing non-Hodgkin lymphoma (NHL) is greatly increased in HIV infection. The aim of this study was to determine whether elevated serum levels of molecules associated with B-cell activation precede the diagnosis of AIDS-associated NHL (AIDS-NHL)., Methods: Serum levels of B-cell activation-associated molecules, interleukin (IL)6, IL10, soluble CD23 (sCD23), sCD27, sCD30, C-reactive protein (CRP), and immunoglobulin E were determined in 179 NHL cases and HIV+ controls in the Multicenter AIDS Cohort Study, collected at up to 3 time points per subject, 0 to 5 years prior to AIDS-NHL diagnosis., Results: Serum IL6, IL10, CRP, sCD23, sCD27, and sCD30 levels were all significantly elevated in the AIDS-NHL group, when compared with HIV+ controls or with AIDS controls, after adjusting for CD4 T-cell number. Elevated serum levels of B-cell activation-associated molecules were seen to be associated with the development of systemic [non-CNS (central nervous system)] NHL, but not with the development of primary CNS lymphoma., Conclusions: Levels of certain B-cell stimulatory cytokines and molecules associated with immune activation are elevated for several years preceding the diagnosis of systemic AIDS-NHL. This observation is consistent with the hypothesis that chronic B-cell activation contributes to the development of these hematologic malignancies., Impact: Marked differences in serum levels of several molecules are seen for several years prediagnosis in those who eventually develop AIDS-NHL. Some of these molecules may serve as candidate biomarkers and provide valuable information to better define the etiology of NHL., (©2011 AACR)

Background: HIV-infected individuals have heightened cancer risk. With the advent of highly active antiretroviral therapy (HAART), the frequency of some AIDS-defining cancers (ADC) has decreased although certain non-AIDS-defining cancers (NADC) are becoming more frequent. Cancers among HIV-infected individuals in Latin American and the Caribbean have not yet been carefully studied., Methods: Cancer cases among the Caribbean, Central and South American network for HIV Research (CCASAnet) cohort were identified reviewing clinical records and pre-existing databases., Results: There were 406 cancers reported: 331 ADC (224 Kaposi sarcomas and 98 non Hodgkin lymphomas). Most frequent NADC (n = 75) were Hodgkin lymphoma and skin cancers. Seventy-three percent of NADC and 45% of ADC were diagnosed >1 year after HIV diagnosis. Fifty-six percent of ADC occurred before HAART start. Median time from HAART start until cancer diagnosis was 2.5 years for NADC and 0.5 years for ADC (P = <0.001). Within 3372 HAART starters, 158 were diagnosed with 165 cancers (82.4% ADC); 85 cases were previous to or concomitant with HAART initiation. Incidence of cancer after HAART initiation in 8080 person-years of follow-up was 7.2 per 1000 person-years (95% confidence interval = 5.5 to 9.3) for ADC and 2.7 (95% confidence interval = 1.8 to 4.1) for NADC; incidence was higher in the first 2 months, particularly for ADC (47.6). A pre-HAART ADC was a predictor of mortality after adjusting for age, sex, and CD4 at HAART initiation., Conclusions: ADC were the most frequent cancers in this region and were often diagnosed close to HIV diagnosis and HAART start. Incidence of cancer was highest around HAART initiation.

Plasmablastic lymphoma (PL) is an uncommon B-cell lymphoma that is strongly associated with human immunodeficiency virus (HIV) infection, and displays distinctive affinity for extranodal presentation in the oral cavity. We report the case of a PL involving the stomach in a 36 year-old man HIV+ patient, associated with Kaposi sarcoma (KS) in sections adjacent to lymphoma. He had a positive history of Castleman disease and KS in a lymphoid node biopsy.

Purpose: Previous studies have shown increased risks of second malignancies after non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL); however, no earlier investigation has quantified differences in risk of new malignancy by lymphoma subtype., Patients and Methods: We evaluated second cancer and leukemia risks among 43,145 1-year survivors of CLL/small lymphocytic lymphoma (SLL), diffuse large B-cell lymphoma (DLBCL), or follicular lymphoma (FL) from 11 Surveillance, Epidemiology, and End Results (SEER) population-based registries during 1992 to 2006., Results: Among patients without HIV/AIDS-related lymphoma, lung cancer risks were significantly elevated after CLL/SLL and FL but not after DLBCL (standardized incidence ratio [SIR], CLL/SLL = 1.42, FL = 1.28, DLBCL = 1.00; Poisson regression P for difference among subtypes, P(Diff) = .001). A similar pattern was observed for risk of cutaneous melanoma (SIR: CLL/SLL = 1.92, FL = 1.60, DLBCL = 1.06; P(Diff) = .004). Acute nonlymphocytic leukemia risks were significantly elevated after FL and DLBCL, particularly among patients receiving initial chemotherapy, but not after CLL/SLL (SIR: CLL/SLL = 1.13, FL = 5.96, DLBCL = 4.96; P(Diff) < .001). Patients with HIV/AIDS-related lymphoma (n = 932) were predominantly diagnosed with DLBCL and had significantly and substantially elevated risks for second anal cancer (SIR = 120.50) and Kaposi's sarcoma (SIR = 138.90)., Conclusion: Our findings suggest that differing immunologic alterations, treatments (eg, alkylating agent chemotherapy), genetic susceptibilities, and other risk factors (eg, viral infections, tobacco use) among lymphoma subtypes contribute to the patterns of second malignancy risk. Elucidating these patterns may provide etiologic clues to lymphoma as well as to the second malignancies.

Importance of the Field: The clinical features and natural history of HIV-associated lymphomas differ greatly from those observed in the general population. The failure to improve outcomes with treatment intensification indicates the need for the introduction of new therapeutic options., Areas Covered in This Review: This review summarizes reports from 1995 to the present which focus on the treatment strategies and their prognostic relevance in the setting of HIV-associated lymphomas., What the Reader Will Gain: The identification of prognostic factors in rare tumors such as HIV-associated lymphomas is going to require the establishment of multi-institutional and cooperative group-supported tissue banks. The rarity of primary effusion lymphomas and plasmablastic lymphomas of the oral cavity type makes large prospective studies difficult and challenges the feasibility of defining therapy specific for a given subpopulation of patients., Take Home Message: HIV-associated lymphomas still represent a relevant field of clinical research. Standard methodologies for therapy in this patient population have yet to be established. However, rituximab plus chemotherapy should be offered to the majority of patients with HIV infection and diffuse large B-cell lymphomas; and the feasibility of intensive aggressive chemotherapy regimens has been successfully tested in HIV-associated Burkitt's lymphomas.

We report 2 patients with HIV-associated non-Hodgkin's lymphoma with massive hepatic involvement and lactic acidosis. The lactic acidosis was likely caused by excessive tumor lactate production coupled with impaired hepatic clearance. Although 1 patient died rapidly, the other survived for 7 months after receiving urgent combination chemotherapy. Clinicians should be aware of this condition and the importance of its early diagnosis and treatment.

Hematopoietic stem cell transplantation (HSCT) replaces a diseased hematopoietic system with a functional, disease-free graft and is frequently used in the treatment of hematologic malignancies. The advent of highly active antiretroviral therapy made it possible to treat medical conditions in HIV-infected patients in the same way as in the general population. Several studies have reported the feasibility, safety, and efficacy of autologous HSCT as rescue or consolidation treatment for non-Hodgkin's and Hodgkin's lymphoma in HIV-infected patients. As a result of the improvements in supportive care and the introduction of attenuated transplant conditioning regimens, allogeneic HSCT has been used to treat life-threatening hematologic disorders, with promising results in HIV-infected patients. Moreover, this strategy has made it possible to treat both the hematologic disease and HIV infection.

Purpose of Review: HIV-infected individuals remain at an increased risk for developing malignancies despite the use of combined antiretroviral therapy. Lymphomas comprise a large proportion of the malignancies that affect the HIV-infected population in developed countries. This review summarizes the recent progress made in HIV lymphoma research published in 2009 through January 2010., Recent Findings: The majority of investigation in this field has been in diffuse large B-cell lymphoma, with infusional therapy remaining promising. Rituximab likely improves complete response and possibly overall survival, but may be associated with increased infections in a subset of patients with very low CD4 cell counts. Risk factors associated with the development of lymphoma include low CD4 cell count and likely cumulative HIV viremia. Biologic insights have been realized regarding pathogenesis., Summary: Overall, the outcome for HIV lymphoma continues to improve as insights into the pathophysiology and treatment advance.

Patients with lymphoma can develop cardiac involvement that includes malignant pericardial effusions and myocardial infiltration, but extensive myocardial invasion by tumor with resultant rupture has been reported only rarely. We report a case of a patient with human immunodeficiency virus and T-cell lymphoma who presented with signs and symptoms that were suggestive of a non-ST-elevation myocardial infarction. Plans were made for cardiac catheterization, but the patient developed thrombocytopenia after the initiation of heparin and eptifibatide. Cardiac catheterization was deferred, and shortly afterwards he had a witnessed cardiac arrest in the hospital and could not be resuscitated. Autopsy revealed transmural infiltration of the myocardium with lymphoma and resultant rupture of the left ventricular free wall. To our knowledge, this is the 1st reported case of left ventricular free-wall rupture due to transmural infiltration by human-immunodeficiency-virus-associated peripheral T-cell lymphoma.We conclude that noncoronary causes of chest pain, including direct myocardial infiltration, should be considered in immunocompromised patients with lymphoma.